Regioselective Synthesis of 2,5-Disubstituted Pyrroles via Stepwise Iododesilylation and Coupling Reactions

A new protocol has been developed for the regioselective preparation of 2,5-disubstituted pyrroles. This approach is based on a stepwise iododesilylation and a subsequent coupling reaction, involving a 6-step pathway starting from the simplest pyrrole. A variety of 2,5-disubstituted pyrrole derivatives are accessible in moderate to good yields. In this study, the protection group for the pyrrole nitrogen is carefully chosen and N, N-dimethylaminosulfonyl is the final choice, which facilitates the subsequent double lithiation and makes the pyrrole moiety more stable. However, the attempted removal of this group fails under several different conditions. Instead, unexpected dimethylaminosulfonyl migration to the beta-position of the pyrrole ring in the presence of tetrabutylammonium fluoride is observed.